Elucidation of the mechanisms which regulate the concentrations of specific enzymes in animal cells will add considerably to our understanding of normal cell function as well as to our understanding of the breakdown of regulatory mechanisms in disease states. We propose to use several glycolytic enzymes (including the isoenzymes of aldolase) and creatine phosphokinase as "markers" to investigate these regulatory mechanisms. Experiments conducted in vivo and with tissue explants in culture will define the importance of regulation of enzyme synthesis and degradation in maintaining the distinctive concentrations of the "marker" enzymes in different cell types. Cell-free protein synthesizing systems and c-DNA-mRNA hybridization experiments will be used to investigate transcriptional and translational regulatory events in detail. Our in vivo and in vitro approaches will be used to investigate how the concentrations of enzymes which function in the same metabolic pathway (i.e. glycolysis) are coordinately regulated and how external information supplied from motor neurons determines the enzyme synthetic programs of muscle cells. Our systems will be directly applied to studying the molecular basis for the reduced rate of synthesis of aldolase and other glycolytic enzymes which we have recently shown to be associated with avian muscular dystrophy.